Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens

NCT07683000 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: GS-US-536-65442025-524336-19
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical study is to compare how effective a long-acting treatment of injectable combination of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) is versus continuing a daily oral HIV treatment in adults with HIV-1 whose virus is already well controlled, after 1 year (52 weeks) of treatment. The primary objective of this study is to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus continuing an oral stable baseline regimen (SBR) in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.

  Week 52

Secondary Outcomes (12)

• Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.

  Week 92

• Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm.

  Week 52

• Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.

  Week 92

• Changes from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 52

  Baseline, Week 52

• Changes from Baseline in CD4+ T-cell Counts at Week 92

  Baseline, Week 92

Study Arms (2)

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

EXPERIMENTAL

Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the study extension phase until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.

Drug: Lenacapavir; Drug: Lenacapavir Tablet; Drug: Teropavimab; Drug: Zinlirvimab

Treatment Group 2: Stable Baseline Regimen (SBR)

EXPERIMENTAL

Participants will continue their SBR through at least Week 92. Oral SBRs will be taken per local prescribing information. After Week 92, eligible participants will have an option to switch to LEN + TAB + ZAB in the study extension phase until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.

Drug: SBR

Interventions

SBR DRUG

SBRs administered orally. SBRs include medicines like bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+ tenofovir alafenamide (TAF)+ emtricitabine (FTC).

Treatment Group 2: Stable Baseline Regimen (SBR)

Lenacapavir DRUG

Administered subcutaneously

Also known as: LEN

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

Lenacapavir Tablet DRUG

Administered orally

Also known as: TAB, GS-5423

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

Teropavimab DRUG

Administered intravenously (IV)

Also known as: TAB, GS-5423

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

Zinlirvimab DRUG

Administered IV

Also known as: GS-2872

Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:
• \) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
• Plasma HIV-1 RNA levels \< 50 copies/mL at screening.
• At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and \< 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is \< 50 copies/mL.
• A plasma HIV-1 RNA test \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior.
• If \> 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
• On a stable oral antiretroviral (ARV) therapy (ART) for ≥ 6 months prior to screening.
• A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be \< 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1.

You may not qualify if:

• History of an opportunistic infection or illness indicative of Stage 3 HIV disease.
• Known hypersensitivity to the study intervention, its metabolites, or formulation excipients.
• Active, serious infections (other than HIV-1) requiring therapy \< 30 days prior to randomization.
• Active tuberculosis infection.
• Acute hepatitis of any cause \< 30 days before randomization.
• History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C).
• Active malignancy requiring acute systemic therapy.
• Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs.
• Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-1.
• Prior use of, or exposure to, long-acting (LA) injectable cabotegravir (CAB) or LA injectable rilpivirine (RPV).
• Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc.
• Current use of, or exposure to, nevirapine or zidovudine.
• Baseline regimen consisting of monotherapy with any single ARV.
• Treatment with immunosuppressant therapies (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) within 4 weeks of screening (with the exception of a single short course of corticosteroids lasting ≤ 7 days) or have a comorbid condition with an anticipated need ongoing immunosuppressive treatment during the study.
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (2)

Be Well Medical Center

Berkeley, Michigan, 48072, United States

RECRUITING

Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)

Annandale, Virginia, 22003, United States

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 6, 2026
• Study Start: July 14, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2033
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)